The plot was based on a dream Ben Falcone had, dreaming about his wife Melissa McCarthy as a fast food worker whose life is falling apart. The two later wrote plot points on napkins before developing the screenplay.
There is only 24 years difference in age between Melissa McCarthy (Tammy) and Susan Sarandon (Tammy's grandmother, Pearl). Furthermore, there is only 11 years difference between McCarthy and Allison Janney, who plays her mother.
Melissa McCarthy and Mark Duplass first met when they were both guests on Jimmy Kimmel Live in Feb 2013. They expressed interest in working together and Melissa contacted Duplass for the role of Bobby when she wrote Tammy.
When Tammy goes back to rescue her grandmother from the nursing home, they are supposed to be in Illinois but all of the vehicles in the parking lot have Kentucky license plates.
When Tammy and Pearl enter the Bar in what is supposed to be Louisville, Kentucky, you can clearly see the North Carolina Flag flying in the background, as this movie was filmed almost entirely in eastern North Carolina.